Evaluation of the pathogenicity of A/H6N1 avian influenza virus and its genetic compatibility with 2009 A/H1N1 pandemic influenza virus in mammalian models

Objective A/H6N1 avian influenza virus has become an epidemic virus in poultry in China,posing a significant threat to public health.In order to evaluate the capacity of pathogenesis and reassortment of H6N1 virus in mammalians,we first evaluated the pathogenicity of H6N1 virus to mice,and then evaluated the compatibility between H6N1 virus and 2009 A/H1N1 pandemic viruse.Methods For the mouse infection experiment,the mice were inoculated intranasally with 101EID50-106EID50 A/H6N1 AIV(A/Mallard/SanJiang/275/2007,which was isolated from wild ducks),and virological and histological data were collected by clinical sign observation,virus titration,and histopathology with HE staining.For the reassorment experiment in guinea pigs,the animals were inoculated with mixed A/H6N1 and A/H1N1 influenza viruses(A/Changchun/01/2009).The nasal washes of guinea pigs were collected every day,and reassortment viruses were obtained by plaque purification and identified by sequence analysis.Results In the mouse infection experiment,the mice were directly infected with H6N1 AIV virus,but were not lethal.The group of mice inoculated with 106 EID50 showed body weight loss,decreased activity,dorsal hair disordered,and tachypnea at day 15 after infection(DPI15).However,the clinical symptoms disappeared at DPI10.The virus titration results showed that the A/H6N1 virus mainly replicated in the lung,trachea and turbinate of mice,and the virus titers were up to 104.5/mL.Using HE staining,the pathological examination found that the lungs of the 106 EID50 group showed pathological changes,including alveolar wall thickening,infiltration of inflammatory cells,fibrin exudation and slight bleeding.In the reassorment experiment of guinea pigs,six reassortant virus strains were recovered with different gene segments derived from H6N1 and H1N1 viruses after three-time plaque purification.The results indicated that A/H6N1 and A/H1N1 influenza virus have high genetic compatibility in mammalian models.Conclusions A/H6N1 AIV can infect mammals directly without adaption and has a high genetic compatibility in guinea pigs with the H1N1 AIV.Therefore,attention should be paid on its significant threat to public health.